A Golgi-targeting fluorescent probe for labile Fe(ii) to reveal an abnormal cellular iron distribution induced by dysfunction of VPS35

Chemical Science
Tasuku HirayamaHideko Nagasawa

Abstract

Iron is involved in numerous physiologically essential processes in our body. However, excessive iron is a pathogenic factor in neurodegenerative diseases, causing aberrant oxidative stress. Divalent metal transporter 1 (DMT1) acts as a primary transporter of Fe(ii) ions. The intracellular delivery of DMT1 toward the cellular membrane via the trans-Golgi network during the endocytotic process is partially regulated by a retromer-mediated protein-sorting system comprising vacuolar protein-sorting proteins (VPSs). Thus, together with DMT1, the Golgi-apparatus acts as a hub organelle in the delivery system for intracellular Fe(ii) ions. Dysfunction of the VPS-relevant protein sorting system can induce the abnormal delivery of DMT1 toward lysosomes concomitantly with Fe(ii) ions. To explore this issue, we developed a fluorescent probe, Gol-SiRhoNox, for the Golgi-specific detection of Fe(ii) ions by integrating our original N-oxide-based Fe(ii)-specific chemical switch, a new Golgi-localizable chemical motif, and polarity-sensitive fluorogenic scaffold. Our synchronous imaging study using Gol-SiRhoNox and LysoRhoNox, a previously developed fluorescent probe for lysosomal Fe(ii), revealed that the intracellular distribution balance ...Continue Reading

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Citations

Sep 12, 2019·Chemical Communications : Chem Comm·Yun Hak LeeKitae Kim
Oct 13, 2019·Angewandte Chemie·Kevin J BruemmerChristopher J Chang
Apr 24, 2020·Cellular and Molecular Neurobiology·Jenny SassoneBarbara Garavaglia
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Jul 31, 2019·Chemical Science·Peng GaoBo Tang
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Jul 1, 2020·Biochimica Et Biophysica Acta. General Subjects·François Foulquier, Dominique Legrand
Aug 6, 2021·Chemical Science·Lijun JiangNicholas J Long
Jan 9, 2021·Journal of the American Chemical Society·Dmytro I DanylchukAndrey S Klymchenko
Nov 18, 2021·Analytical Methods : Advancing Methods and Applications·Ejaj AhmmedPabitra Chattopadhyay

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Methods Mentioned

BETA
fluorescence imaging
amidation
Fluorescence
confocal microscopy
fluorescence microscopy
transfection

Software Mentioned

Gol
SiRhoNox

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